1 Center for Medical Science Research, College of Medicine, Hallym University, Gangwon-do, Republic of Korea, 2 Department of Microbiology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea, 3 Department of Pathology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea, 4 Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk, Republic of Korea

Abstract

Whole-virus vaccines, including inactivated or live-attenuated influenza vaccines, have been conventionally developed and supported as a prophylaxis. These currently available virus-based influenza vaccines are widely used in the clinic, but the vaccine production takes a long time and a huge number of embryonated chicken eggs. To overcome the imperfection of egg-based influenza vaccines, epitope-based peptide vaccines have been studied as an alternative approach. Here, we formulated an efficacious peptide vaccine without carriers using phosphodiester CpG-DNA and a special liposome complex. Potential epitope peptides predicted from the hemagglutinin (HA) protein of the H5N1 A/Viet Nam/1203/2004 strain (NCBI database, AAW80717) were used to immunize mice along with phosphodiester CpG-DNA co-encapsulated in a phosphatidyl-β-oleoyl-γ-palmitoyl ethanolamine (DOPE):cholesterol hemisuccinate (CHEMS) complex (Lipoplex(O)) without carriers. We identified a B cell epitope peptide (hH5N1 HA233 epitope, 14 amino acids) that can potently induce epitope-specific antibodies. Furthermore, immunization with a complex of the B cell epitope and Lipoplex(O) completely protects mice challenged with a lethal dose of recombinant H5N1 virus. These results suggest that our improved peptide vaccine technology can be promptly applied to vaccine development against pandemic influenza. Furthermore our results suggest that potent epitopes, which cannot be easily found using proteins or a virus as an antigen, can be screened when we use a complex of peptide epitopes and Lipoplex(O).

Funding: This research was supported by a grant from the Korea Healthcare Technology R&D Project of the Korean Ministry for Health, Welfare and Family Affairs (A08-4411-BB2004-08N1-00030B) and grants from the National Research Foundation (20090081761, 20090083296), which is funded by the Korean Ministry of Education, Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.